WO2021041667A1 - Modification de messages stockés dans des mélanges de molécules à l'aide d'une chromatographie sur couche mince - Google Patents

Modification de messages stockés dans des mélanges de molécules à l'aide d'une chromatographie sur couche mince Download PDF

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Publication number
WO2021041667A1
WO2021041667A1 PCT/US2020/048190 US2020048190W WO2021041667A1 WO 2021041667 A1 WO2021041667 A1 WO 2021041667A1 US 2020048190 W US2020048190 W US 2020048190W WO 2021041667 A1 WO2021041667 A1 WO 2021041667A1
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Prior art keywords
molecules
subset
molecule
readable medium
machine
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PCT/US2020/048190
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English (en)
Inventor
George M. Whitesides
Albert Siangyoong WONG
Michael Johannes FINK
Khaled Abdelazim MOHAMED
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President And Fellows Of Harvard College
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Priority to EP20775095.1A priority Critical patent/EP4022300A1/fr
Publication of WO2021041667A1 publication Critical patent/WO2021041667A1/fr
Priority to US17/681,155 priority patent/US11989619B2/en

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    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06K—GRAPHICAL DATA READING; PRESENTATION OF DATA; RECORD CARRIERS; HANDLING RECORD CARRIERS
    • G06K7/00—Methods or arrangements for sensing record carriers, e.g. for reading patterns
    • G06K7/10—Methods or arrangements for sensing record carriers, e.g. for reading patterns by electromagnetic radiation, e.g. optical sensing; by corpuscular radiation
    • G06K7/14—Methods or arrangements for sensing record carriers, e.g. for reading patterns by electromagnetic radiation, e.g. optical sensing; by corpuscular radiation using light without selection of wavelength, e.g. sensing reflected white light
    • G06K7/1404—Methods for optical code recognition
    • G06K7/1408—Methods for optical code recognition the method being specifically adapted for the type of code
    • G06K7/1434—Barcodes with supplemental or add-on codes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/90—Plate chromatography, e.g. thin layer or paper chromatography
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06K—GRAPHICAL DATA READING; PRESENTATION OF DATA; RECORD CARRIERS; HANDLING RECORD CARRIERS
    • G06K19/00—Record carriers for use with machines and with at least a part designed to carry digital markings
    • G06K19/06—Record carriers for use with machines and with at least a part designed to carry digital markings characterised by the kind of the digital marking, e.g. shape, nature, code
    • G06K19/06009—Record carriers for use with machines and with at least a part designed to carry digital markings characterised by the kind of the digital marking, e.g. shape, nature, code with optically detectable marking
    • G06K19/06037—Record carriers for use with machines and with at least a part designed to carry digital markings characterised by the kind of the digital marking, e.g. shape, nature, code with optically detectable marking multi-dimensional coding
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06K—GRAPHICAL DATA READING; PRESENTATION OF DATA; RECORD CARRIERS; HANDLING RECORD CARRIERS
    • G06K19/00—Record carriers for use with machines and with at least a part designed to carry digital markings
    • G06K19/06—Record carriers for use with machines and with at least a part designed to carry digital markings characterised by the kind of the digital marking, e.g. shape, nature, code
    • G06K19/06009—Record carriers for use with machines and with at least a part designed to carry digital markings characterised by the kind of the digital marking, e.g. shape, nature, code with optically detectable marking
    • G06K19/06046—Constructional details
    • G06K19/06056—Constructional details the marking comprising a further embedded marking, e.g. a 1D bar code with the black bars containing a smaller sized coding
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06K—GRAPHICAL DATA READING; PRESENTATION OF DATA; RECORD CARRIERS; HANDLING RECORD CARRIERS
    • G06K19/00—Record carriers for use with machines and with at least a part designed to carry digital markings
    • G06K19/06—Record carriers for use with machines and with at least a part designed to carry digital markings characterised by the kind of the digital marking, e.g. shape, nature, code
    • G06K19/06009—Record carriers for use with machines and with at least a part designed to carry digital markings characterised by the kind of the digital marking, e.g. shape, nature, code with optically detectable marking
    • G06K19/06046—Constructional details
    • G06K19/06084—Constructional details the marking being based on nanoparticles or microbeads
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06K—GRAPHICAL DATA READING; PRESENTATION OF DATA; RECORD CARRIERS; HANDLING RECORD CARRIERS
    • G06K19/00—Record carriers for use with machines and with at least a part designed to carry digital markings
    • G06K19/06—Record carriers for use with machines and with at least a part designed to carry digital markings characterised by the kind of the digital marking, e.g. shape, nature, code
    • G06K19/06009—Record carriers for use with machines and with at least a part designed to carry digital markings characterised by the kind of the digital marking, e.g. shape, nature, code with optically detectable marking
    • G06K19/06046—Constructional details
    • G06K19/0614—Constructional details the marking being selective to wavelength, e.g. color barcode or barcodes only visible under UV or IR
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06K—GRAPHICAL DATA READING; PRESENTATION OF DATA; RECORD CARRIERS; HANDLING RECORD CARRIERS
    • G06K19/00—Record carriers for use with machines and with at least a part designed to carry digital markings
    • G06K19/06—Record carriers for use with machines and with at least a part designed to carry digital markings characterised by the kind of the digital marking, e.g. shape, nature, code
    • G06K19/06009—Record carriers for use with machines and with at least a part designed to carry digital markings characterised by the kind of the digital marking, e.g. shape, nature, code with optically detectable marking
    • G06K19/06046—Constructional details
    • G06K19/06178—Constructional details the marking having a feature size being smaller than can be seen by the unaided human eye
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00659—Two-dimensional arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/0068—Means for controlling the apparatus of the process
    • B01J2219/00695—Synthesis control routines, e.g. using computer programs
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00725—Peptides
    • G—PHYSICS
    • G11—INFORMATION STORAGE
    • G11B—INFORMATION STORAGE BASED ON RELATIVE MOVEMENT BETWEEN RECORD CARRIER AND TRANSDUCER
    • G11B7/00—Recording or reproducing by optical means, e.g. recording using a thermal beam of optical radiation by modifying optical properties or the physical structure, reproducing using an optical beam at lower power by sensing optical properties; Record carriers therefor
    • G11B7/24—Record carriers characterised by shape, structure or physical properties, or by the selection of the material
    • G11B7/241—Record carriers characterised by shape, structure or physical properties, or by the selection of the material characterised by the selection of the material
    • G11B7/242—Record carriers characterised by shape, structure or physical properties, or by the selection of the material characterised by the selection of the material of recording layers
    • G11B7/244—Record carriers characterised by shape, structure or physical properties, or by the selection of the material characterised by the selection of the material of recording layers comprising organic materials only

Definitions

  • Embodiments of the present disclosure relate to storage media, and more specifically, to modifying messages stored in mixtures of molecules using thin-layer chromatography.
  • a substrate has an array of addressable locations thereon, each addressable location adapted to be physically associated with a collection of molecules, each collection comprising at least a first subcollection of molecules and a second subcollection of molecules.
  • the molecules in the collection are selected from a set of unambiguously identifiable molecules, the set comprising at least a first subset of molecules and a second subset of molecules.
  • Each molecule in the first subset is identifiable by a first physical property
  • each molecule in the second subset is identifiable by a second physical property, different from the first physical property.
  • Each molecule in the set is uniquely associated with a predetermined position in a numerical value, wherein the presence of the molecule in the collection indicates a predetermined digit at the associated position and the absence of said molecule in the collection indicates a zero at said associated position.
  • a molecule is uniquely associated with a position when it is associated with exactly one position, irrespective of whether that position is associated with one or more than one molecule. In other words, in various embodiments described herein, more than one molecule can be associated with the same position.
  • a numerical value comprising a set of digit/position pairs is received, the set comprising at least a first subset of digit/position pairs, and a second subset of digit/position pairs.
  • An association between at least the first and the second subsets of digit/position pairs and the set of digit/position pairs is received.
  • a one-to-one association between at least the first subset of digit/position pairs and a first subset of molecules, and the second subset of digit/position pairs and a second subset of molecules is received, the first and the second subsets of molecules each selected from a set of unambiguously identifiable molecules, wherein each molecule in the first subset is identifiable by a first physical property, and each molecule in the second subset is identifiable by a second physical property, different from the first physical property.
  • a collection of molecules corresponding to the numerical value is determined.
  • Determining the collection comprises: determining at least a first subcollection of molecules corresponding to the first subset of digit/position pairs, and a second subcollection of molecules corresponding the second subset of digit/position pairs, and including at least the first and the second subcollections into the collection of molecules.
  • the molecules of the collection are physically associated with a substrate of the machine-readable medium at an addressable location thereon.
  • a one-to-one association between at least the first subset of digit/position pairs and a first subset of molecules, and the second subset of digit/position pairs and a second subset of molecules is received, the first and the second subset of molecules selected from a set of unambiguously identifiable molecules, wherein each molecule in the first subset is identifiable by a first physical property, and each molecule in the second subset is identifiable by a second physical property, different from the first physical property.
  • a collection of molecules physically associated with a substrate of the machine-readable medium at an addressable location thereon is received, the collection comprising at least a first subcollection of molecules selected from the first subset of molecules, and a second subcollection of molecules, selected from the second subset of molecules.
  • a numerical value comprising the set of digit/position pairs from the collection of molecules is determined. Determining the numerical value comprises: setting each position of the first subset of digit/position pairs to the digit whose associated molecule is present in the first subcollection. Each position of the second subset of digit/position pairs is set to the digit whose associated molecule is present in the second subcollection. The first and the second subsets of digit/position pairs are combined.
  • each molecule of the set is a polymer or oligomer. In some embodiments, each molecule of the set is a non-polymeric molecule. In some embodiments, each molecule of the set of unambiguously identifiable molecules is associated with a binary digit.
  • the numerical value has a radix and a predetermined number of positions. In some embodiments, the numerical value is a binary value having a predetermined number,N, of bits. In some embodiments, the numerical value is a binary value having 32 bits.
  • each collection encodes a bit string.
  • the bit string encodes an ASCII value.
  • each molecule in the set is unambiguously identifiable by its polarity. In some embodiments, each molecule in the set is unambiguously identifiable by its thin-layer chromatography (TLC) retardation factor (Rf). In some embodiments, the first physical property is an iodine (I2) reactivity and the second physical property is UV fluorescence.
  • TLC thin-layer chromatography
  • Rf retardation factor
  • the first physical property is an iodine (I2) reactivity
  • the second physical property is UV fluorescence.
  • each molecule in the collection is linked to the substrate at the respective addressable location. In some embodiments, each molecule in the collection is covalently attached to the substrate at the respective addressable location. In some embodiments, each molecule in the collection is non-covalently attached to the substrate at the respective addressable location.
  • a substrate has an array of addressable locations thereon, each addressable location adapted to be physically associated with a collection of molecules, each collection comprising at least a first subcollection of molecules and a second subcollection of molecules.
  • the molecules in the collection are selected from a set of unambiguously identifiable molecules, the set comprising at least a first subset of molecules and a second subset of molecules. At least one molecule of the first subset is chemically convertible into at least one molecule of the second subset.
  • Each molecule in the first subset and each molecule of the second subset is identifiable by a physical property.
  • Each molecule in the set is associated with a predetermined position in a numerical value, wherein the presence of the molecule in the collection indicates a predetermined digit at the associated position and the absence of said molecule in the collection indicates a zero at said associated position.
  • the first subset and the second subset are disjoint.
  • disjoint subsets are subsets having no common elements.
  • each molecule in the set is uniquely associated with the predetermined position in a numerical value.
  • the at least one molecule of the first subset is chemically reversibly convertible into the at least one molecule of the second subset.
  • a numerical value comprising a set of digit/position pairs is received, the set comprising at least a first subset of digit/position pairs, and a second subset of digit/position pairs.
  • An association between at least the first and the second subsets of digit/position pairs and the set of digit/position pairs is received.
  • An association between at least the first subset of digit/position pairs and a first subset of molecules, and the second subset of digit/position pairs and a second subset of molecules is received.
  • At least one molecule of the first subset is chemically convertible into at least one molecules of the second subset, the first and the second subsets of molecules each selected from a set of molecules unambiguously identifiable by a physical property.
  • a collection of molecules corresponding to the numerical value is determined. Determining the collection comprises: determining at least a first subcollection of molecules corresponding to the first subset of digit/position pairs, and a second subcollection of molecules corresponding the second subset of digit/position pairs, and physically associating the molecules of the first subcollection with a substrate of the machine-readable medium at an addressable location thereon. At least one molecule of the first subcollection of molecules is chemically converted into at least one molecule of the second subcollection of molecules.
  • each molecule of the set is a polymer or oligomer. In some embodiments of the machine- readable medium or the method, each molecule of the set is a polypeptide.
  • chemically converting includes enzymatically modifying at least one molecule. In some embodiments of the machine-readable medium or the method, chemically converting includes at least one of acetylating, deacetylating, phosophorylating, and dephosphorylating.
  • each molecule of the set of unambiguously identifiable molecules is associated with a binary digit.
  • the numerical value has a radix and a predetermined number of positions. In some embodiments of the machine-readable medium or the method, the numerical value is a binary value having a predetermined number, N , of bits. In some embodiments of the machine-readable medium or the method, the numerical value is a binary value having 32 bits. In some embodiments of the machine-readable medium or the method, each collection encodes a bit string. In some embodiments of the machine-readable medium or the method, the bit string encodes an ASCII value.
  • each molecule in the set is unambiguously identifiable by a mass spectrometry.
  • each molecule in the collection is linked to the substrate at the respective addressable location.
  • each molecule in the collection is covalently attached to the substrate at the respective addressable location.
  • each molecule in the collection is non-covalently attached to the substrate at the respective addressable location.
  • Fig. 1A is a graph of retardation factor (Rf) of exemplary molecules for encoding information according to embodiments of the present disclosure.
  • Fig. IB is an image of an exemplary developed Thin-Layer Chromatography (TLC) plate encoding information according to embodiments of the present disclosure.
  • Fig. 2A is a schematic illustration of 16 exemplary MolBits for encoding information according to embodiments of the present disclosure.
  • Fig. 2B is a graph of retardation factor (Rf) illustrating sets of MolBits for encoding information according to embodiments of the present disclosure.
  • Fig. 2C is an image of an exemplary developed Thin-Layer Chromatography (TLC) plate encoding information according to embodiments of the present disclosure.
  • Fig. 2D is a schematic view of an exemplary text conversion of information encoded according to embodiments of the present disclosure.
  • Fig. 3 is a schematic view of subsets and associated QR codes encoding information according to embodiments of the present disclosure.
  • Fig. 4 is a set of graphs of retardation factor (Rf) of exemplary molecules for encoding information according to embodiments of the present disclosure.
  • Fig. 5A-5B are images of an exemplary Thin-Layer Chromatography (TLC) plate encoding information according to embodiments of the present disclosure.
  • Fig. 6A is a set of densitograms of Thin-Layer Chromatography (TLC) plates developed over different separation lengths according to embodiments of the present disclosure.
  • Fig. 6B is a graph of retardation factor (Rf) showing the influence of separation length according to embodiments of the present disclosure.
  • Fig. 7 is an image of an exemplary Thin-Layer Chromatography (TLC) plate encoding information according to embodiments of the present disclosure.
  • TLC Thin-Layer Chromatography
  • Fig. 8A-B are exemplary QR codes according to embodiments of the present disclosure.
  • Fig. 8C are images of exemplary Thin-Layer Chromatography (TLC) plates encoding information according to embodiments of the present disclosure.
  • Fig. 9 illustrates a method for writing data to a machine-readable medium is illustrated according to embodiments of the present disclosure.
  • Fig. 10 illustrates a method for reading data from a machine-readable medium is illustrated according to embodiments of the present disclosure.
  • Fig. 11A-C illustrate bit modifications using SAMDI according to embodiments of the present disclosure.
  • Fig. 12A-C illustrate bit modifications using TLC according to embodiments of the present disclosure.
  • Fig. 13 illustrates layered decoding, using combinations of sequential reactions according to embodiments of the present disclosure.
  • Fig. 14A-D illustrate mixture of MolBits according to embodiments of the present disclosure.
  • Fig. 15 is a graph of intensity against pH according to embodiments of the present disclosure.
  • Fig. 16 depicts a computing node according to embodiments of the present disclosure.
  • bit strings upon readout could enable strategies to enhance the security in data storage.
  • Established methods used, for example, in tracking of transactions (“fingerprinting”), copyright protection, and authentication — reveal a hidden message based on how the information is read (e.g ., watermarking, secretly embedded tags in stored data, or steganography, hiding the data altogether) and provide a non- obvious layer of protection. While it is classified as a weak form of security, it can complement cryptography (stronger security, but computationally more expensive), which is intended to completely prevent unauthorized access to data.
  • Examples of embedding secondary data or generating sequence-dependent messages in (bio)chemical methods include hiding a key DNA-sequence among dummy sequences, growth-media- dependent protein expression, and the use of an indicator to discriminate among different chemical inputs. These concepts, require sophisticated methods to encode information (e.g., using DNA strands, or a molecule comprising different fluorophores), limiting the scalability and flexibility of the method to change the meaning of a message.
  • SAMDI mass spectrometry
  • the presence or absence of a molecule represents a “1” or a “0” in a binary string of information, and the sequence of digits is determined by a molecular property that all MolBits of the mixture possess ( e.g ., mass).
  • TLC thin layer chromatography
  • Fig. 1 illustrates the encoding of information using Thin-Layer Chromatography according to embodiments of the present disclosure.
  • molecules 1-8, separated on a TLC plate, are identified by their characteristic retardation factors ( R/ ).
  • the error bars show the uncertainty of Rf -values based on a triplicate experiment.
  • the inset shows an example of a mixture comprising all eight molecules, separated on a TLC plate and visualized under UV irradiation at 254 nm.
  • Fig. IB shows a developed TLC plate comprising 12 lanes, each with a mixture of molecules 1-8. The binary data based are depicted below the TLC plate. Binary-to-ASCII conversion results in the message ‘HELLO WOLRD’.
  • TLC plates were developed using dichloromethane/ methanol (20: 1) as the mobile phase and processed as described in the Methods.
  • the letter “g” (the 103 rd symbol in ASCII, converted to the binary bit string 01100111 as a representation of 0-2 7 + 2 6 + 2 5 + 0-2 4 + 0-2 3 + 2 2 + 2 1 + 2°) is the mixture 7 + 6 + 3 + 2 + 1 (see Table 1).
  • a sample containing an appropriate mixture of the molecules 1-8 on the TLC plate (Fig. 5).
  • Fig. IB shows an example of a developed plate, visualized under UV light (at 254 nm), with 12 mixtures, each containing a specific combination of the molecules 1-8, in 12 parallel lanes.
  • the rightmost lane contains all eight compounds and serves as a reference for the expected / ⁇ values of separated Molbits.
  • a binary-to-ASCII conversion of the MolBits contained in the other 11 lanes revealed the message HELLO WORLD.
  • short messages can be encoded in mixtures of MolBits using polarity of molecules to indicate the sequence of digits in a binary representation.
  • FIG. 2 illustrates decoding information using different visualization techniques according to embodiments of the present disclosure.
  • Fig. 2A is an illustration of 16 MolBits that separates into eight ‘sets’ of Rf values I- VIII. Sets IV and V, serve as examples of how each set can be built up from multiple MolBits that can be readout differently using various visualization methods. See Fig. 7 for the summary of the full screening.
  • Fig. 2B shows MolBits 5, 7, 9-13, 16 separated on a TLC plate and visualized under iodine (I2) and UV irradiation at 254 nm. The functional group that is stained with I2 (red), or visualized with UV (grey), is highlighted in the chemical structures.
  • I2 iodine
  • FIG. 2C shows a developed TLC plate comprising 11 lanes, each with a mixture of molecules 5, 7, 9-13, 16, read out using I2 and UV.
  • Fig. 2D shows the binary from Fig. 2C converted into text using a four-digit or eight-digit lookup table (hex, and ASCII, respectively). The presence of a MolBit is indicated by a closed circle, the absence of a MolBit is indicated by an open circle. MolBits that are invisible to the corresponding stain are not circled. [0061] Chemoselective staining enables control over the read-out of mixtures that comprise multiple MolBits at the same A/values (Fig. 2A).
  • UV irradiation and (common) chemoselective methods such as, iodine vapor (I2), bromocresol green (BCG), ninhydrin, or potassium permanganate (KMnCri) — to visualize
  • 2C shows two developed plates, with 11 mixtures, each containing a specific combination of the set (5, 7, 9-13, 16 ⁇ , visualized with iodine (I2) and under UV light (at 254 nm).
  • the reference lanes validate that compounds 5, 7, 13, 16 are not visible when the plate is stained with I2, and 9-12 are not visible under UV.
  • Each lane thus encodes a 4-bit string, which can represent any hexadecimal symbol (0, 1,..., 9, A,..., F).
  • the same set of four mixtures on one plate can be decoded to “164417744” when visualized with I2, and to “8DB0F9CAA” when visualized with UV (Fig. 2D).
  • the use of other visualization methods especially those that stain the TLC plate irreversibly, could be used to prohibit reading parts of the message, at least by colorimetric detection.
  • Fig. 3 illustrates selection of a subset from a subset according to embodiments of the present disclosure. Illustration of subsetting form a mixture of MolBits (using UV) compared to subsetting from a subset (using I2, and UV, sequentially). The developed TLC plates were cropped and inserted in the QR code to reveal the information that was masked “Time: [December 2019], Location: [Washington, D.C.]”. See Fig. 8 for details of the pattern substitution with TLC plates.
  • the readout can be modified by selecting a subset based on sequential staining. For instance, compounds 9-12 do not absorb UV light, but become visible under UV after they have been treated with iodine.
  • the lanes that contain one of the pair of molecules with orthogonal properties, or both, will show as a spot.
  • the bit string in lane 1 changes from “1000” to “1001”, and in lane 2 changes from “1011” to “1111”, etc., which means that the message “8DB0F9CAA” changed into “9FF4FFFEE” (Fig. 7).
  • QR Quick Response
  • the secured information of the QR code (here, the time and location of an event) is initially unreadable because a part of the pattern was masked.
  • the mask was lifted (or more precisely, replaced) by incorporating the pattern on the TLC plate, but only when it was visualized with I2 followed by UV.
  • a standard QR code reading app on a smartphone is capable of decoding the pattern, even when the spots were offset ( e.g. , the two right most lanes).
  • the incorporation of patterns that were visualized with either UV or I2 (Fig. 8) alone did not reveal the encoded information.
  • the use of sequential staining (or more generally, chemical reactions) thus allows subsetting from a subset , in this case, to reveal, but more generally to modify the meaning of a message.
  • the present disclosure demonstrates the encoding of short messages using mixtures of MolBits using the molecular properties polarity and chemical reactivity to indicate the sequence of digits in a binary representation.
  • Simple staining chemistry was used to alter the read-out of the information in ways that allowed a single spot (as separated by TLC) to be resolved into multiple bits.
  • data in the encoded information can be hidden (by using mixtures with additional MolBits at the same Rf s) and modified (by reading out the same mixture with different stains sequentially, and depending on the order of the sequence).
  • ninhydrin staining of amines represents a logical AND operation, since the output color is only produced when both inputs amine and ninhydrin are present — the features we presented here are not designed to act as molecular logic gates, which ideally would have compatible inputs and outputs to enable the formation of logic circuits.
  • Our strategy integrates the processes of encoding and decoding of short messages, based on molecular properties that can easily be exploited by established chemical concepts and methods, such as chromatographic separation, miscibility, and functional- group-specific staining.
  • TLC chromatographic capacity
  • sensitivity to visualization but could logically and practically be extended to other existing technology, including separation methods with a higher resolution than that of TLC (e.g ., high-performance liquid chromatography, gas chromatography, capillary electrophoresis).
  • TLC does, however, not require any power to operate, is available in virtually any chemical laboratory, and can easily be employed in resource-limited settings, including staining operations. These characteristics set it apart from more sophisticated technology, and its simplicity enables the quick exploration and development of new contributions to molecular systems that store and process information.
  • TLC plate preparation Samples containing an appropriate mixture of compounds (each dissolved in methanol, 20 mM) were deposited on the TLC plates (1 cm from the bottom edge). Each lane is separated by a distance of 0.5 cm. The plate sizes varied: For a typical experiment (separation length, 4 cm, and lanes, 12), we used a 6x8 cm plate (4x6 cm is required for separation, and additional 1 cm from each edge is required for a reproducible separation). Analyte was drawn from a sample (typically ⁇ 0.1 pL) and deposited it onto a TLC plate as a spot, using glass capillaries tubes. The solvent is allowed to evaporate completely after deposition, to prevent it from interfering with sample's interactions with the mobile phase during the development of the TLC.
  • TLC plates are visualized by illumination with UV light at a wavelength of 254 nm (the adsorbent layer fluoresces light green under UV light, unless the presence of compounds quenches the fluorescence), and/or visualized using standard TLC staining techniques.
  • the stains were prepared following literature procedure and applied by immersing the plate in the appropriate solution.
  • Bromocresol green (BCG), and ninhydrin react specifically with functional groups on the compounds: BCG deprotonates a carboxylic acid, and ninhydrin exclusively reacts with primary and secondary amines.
  • Potassium manganese (KMnCri) and iodine (I2) are less selective than BGC and ninhydrin.
  • Image processing and conversion into Rf values We photographed the plates, stained or visualized with UV, using a smartphone camera. Image processing steps include split color, enhance contrast, image-to-densitogram conversion, // / analysis, and were performed using National Institutes of Health (NIH) ImageJ, as follows: i) The original image is separated into red, green, and blue channels using function run("Split Channels”) ii) Subsequently, the image from the green (when visualized with UV) or blue channel (when visualized with a stain) was selected, cropped, and the contrast is enhanced iii) The image is viewed by an array of lines (one line per lane), using functions makeLine(xi, yi, X2, y2) and roiManager(”Add') for each lane, and converted into a set of densitograms, using functions roiManager("Multi Plot”) iv) Finally, the pixel positions p are converted into retardation factor/?/ values: /
  • Fig. 4 illustrates compound classes separated by TLC and ordered by their retardation factors. Compounds used as Molbits 1-8 in the main text are indicated by a circle. Classes of compounds were screened and MolBits were selected for their differential polarity.
  • Fig. 5 shows a TLC plate encoding HELLO WORLD.
  • Fig. 5A shows the plate before mixtures of MolBits 1-8 were separated.
  • Fig. 5B shows the plate after they were separated but visualized with iodine.
  • TLC plates Examples of TLC plates. TLC plates, undeveloped and stained with iodine, depicted in Fig. 5 show the supplementary information of main text Fig. 1.
  • Fig. 6 illustrates Determination of the resolution of separations based on TLC.
  • Fig. 6A shows densitograms of TLC plates developed over different separation lengths.
  • Fig. 6B shows the influence of separation length on the retardation factor Rf. Time required for the solvent front to development of the plates is given in the insert.
  • TLC provides an information density of at least 8 bit per lane, which on a plate of 10.0x6.0 cm equals to 2.1 bits per cm 2 (based on 16 lanes, separated by 0.5 cm).
  • the density can be increased by 4-fold, if spot sizes are reduced, achieved with ultrafme capillaries tubes (see Methods), and additional MolBit 9-16 are incorporated.
  • Table 1 lists Writable symbols, used for encoding ‘ASCII characters’ in mixtures of molecules.
  • Table 2 lists hex symbols, used for encoding with MolBits 5, 7, 9-13, 16.
  • Table 3 provides a summary of visualization of MolBits 1-16 with staining solutions. UV irradiation at 254 nm, Iodine (I2), Bromocresol green (BCG), Ninhydrin, and Potassium Permanganate (KMn04).
  • FIG. 7 shows TLC plate (used in Fig. 2C) that was visualized with UV, after it was stained with I2.
  • Binary-to-hex conversion shows that the originally message ‘8DB0F9CAA’ (in UV) changes into ‘9FF4FFFEE’ due to the appearance of additional spots.
  • Fig. 8 shows Pattern substitution in a QR code, using TLC.
  • Fig. 8A shows the mask (in grey) that was used to block the decoding of the information encrypted with a QR code.
  • Fig. 8B shows developed TLC plates visualized using I2, inserted in the QR code.
  • Fig. 8C shows pattern substitution used for the two types of visualization methods (in grey and red, corresponding to UV and I2), and the sum of both methods (in black).
  • Encoding of patterns using TLC The patterns depicted in Fig. 8 are encoded in mixtures of MolBits of the set (2, 3, 5, 6, 9-11, 13-15 ⁇ . We detailed the composition for each lane in Table 3.
  • Table 4 lists the composition of MolBits for substituting the masked pattern in the QR code in Fig. 3.
  • a method for writing data to a machine-readable medium is illustrated according to embodiments of the present disclosure.
  • a numerical value comprising a set of digit/position pairs is received, the set comprising at least a first subset of digit/position pairs, and a second subset of digit/position pairs.
  • an association between at least the first and the second subsets of digit/position pairs and the set of digit/position pairs is received.
  • a one-to-one association between at least the first subset of digit/position pairs and a first subset of molecules, and the second subset of digit/position pairs and a second subset of molecules is received, the first and the second subsets of molecules each selected from a set of unambiguously identifiable molecules, wherein each molecule in the first subset is identifiable by a first physical property, and each molecule in the second subset is identifiable by a second physical property, different from the first physical property.
  • a collection of molecules corresponding to the numerical value is determined.
  • Determining the collection comprises: determining at least a first subcollection of molecules corresponding to the first subset of digit/position pairs, and a second subcollection of molecules corresponding the second subset of digit/position pairs, and including at least the first and the second subcollections into the collection of molecules.
  • the molecules of the collection are physically associated with a substrate of the machine-readable medium at an addressable location thereon.
  • a method for reading data from a machine-readable medium is illustrated according to embodiments of the present disclosure.
  • an association between a set of digit/position pairs and at least a first and a second subsets of digit/position pairs is received.
  • a one-to-one association between at least the first subset of digit/position pairs and a first subset of molecules, and the second subset of digit/position pairs and a second subset of molecules is received, the first and the second subset of molecules selected from a set of unambiguously identifiable molecules, wherein each molecule in the first subset is identifiable by a first physical property, and each molecule in the second subset is identifiable by a second physical property, different from the first physical property.
  • a collection of molecules physically associated with a substrate of the machine-readable medium at an addressable location thereon is received, the collection comprising at least a first subcollection of molecules selected from the first subset of molecules, and a second subcollection of molecules, selected from the second subset of molecules.
  • a numerical value comprising the set of digit/position pairs from the collection of molecules is determined. Determining the numerical value comprises: setting each position of the first subset of digit/position pairs to the digit whose associated molecule is present in the first subcollection. Each position of the second subset of digit/position pairs is set to the digit whose associated molecule is present in the second subcollection.
  • the first and the second subsets of digit/position pairs are combined.
  • SAMDI-MS using reaction ‘pairs ’ to introduce reversible changes in a molecular property.
  • Fig. 11 illustrates bit modifications using SAMDI.
  • SAMDI allows for selective and reversible modifications of information bits by chemically or enzymatically modifying the reactive side chains of individual oligopeptides.
  • acetylation/deacetylation could form a pair of reactions to change the mass of the MolBit (on a 384 well plate, Fig. 11B), and allow one book title to change into another (Fig. 11C).
  • each well contain an oligopeptide CRGKAG, or an acetylated oligopeptide CRGKAcAG.
  • acetic anhydride (Ac20) to acetylate — to add 42 Daltons to the initial mass — and thus change a ‘O’ (presence of a signal from the compound in the pre-determined window) into a ‘ G .
  • KDACs lysine deacetylases
  • KDACs deacetylates (removal of an acetyl- group) to change a ‘ G into a ‘O’ .
  • KDACs lysine deacetylases
  • Combining this approach with other pairs of reactions would allows for the modification of any information written using these set of peptides to be changed to any other information.
  • Other enzymes or pairs of reactions that can be used are, such as Phosphorylation/Dephosphorylation.
  • TLC Using functional group specific reactions to filter molecular properties.
  • Fig. 12 illustrates bit modifications using TLC.
  • Fig. 12A illustrates encoding information using Thin-Layer Chromatography (TLC).
  • Fig. 12B illustrates decoding information using different visualization techniques.
  • TLC is a convenient method to separate a relatively small number of molecules on a small plate based on their polarity. It is easily applicable to sets of eight molecules (1 byte), as shown here, or perhaps up to 16 (2 bytes). It is a technique that is inexpensive, simple, requires no power or complex instrumentation, and — importantly — it can use different modes of visualization, e.g ., absorbance, fluorescence, or chemical staining.
  • Fig. 12A illustrates the separation process into a set of eight distinguishable groups of molecules (rather than eight distinguishable molecules).
  • Each group chromatographic spots at predefined retardation factor Rf values
  • Rf values can contain multiple MolBits with differences in their functional groups (but not polarity), that can be addressed by different chemical stains (Fig. 12B), and thus allows visualization methods (e.g, absorbance, or chemical staining reagents) to be used as a ‘filter’ to modify the read out of the bit strings on the plate (illustrated by Fig. 12C).
  • Fig. 13 illustrates layered decoding, using combinations of sequential reactions.
  • Reactions change either a molecular property that all MolBits of the mixture possess (e.g, mass, or polarity) or a specific property of that only a few MolBits of the mixture possesses (e.g, functional groups).
  • TLC can be used to reveal short messages (temporarily, or permanently) and provides control over revealing one meaning or another by using chemical stains, whereas SAMDI allows for the reversible modifications of any information using enzymatic reactions.
  • the two approaches differ in the property used for separation (polarity or mass) and the specificity of the subsetting reaction (low specificity with stains, high specificity with enzymes), as well as the accuracy/resolution in detection (retardation factor on a TLC plate, and millidalton resolution in mass spectrometry).
  • the SAMDI-MS approach is superior to the TLC approach in terms of reading speed, writing speed, storage density, and longevity but, however, is not equipped with a number of high-yield selective chemical and enzymatic reactions.
  • Reactions can be carried out sequentially to creates layers of modifications, and thus layers of encryption.
  • the ability to modify bits can be used (either by changing a property, or filtering of a property) to develop a reaction scheme.
  • the inclusion of reactions in the encoding and decoding of information allows the use of a “lookup-tree” for defining alphanumerical symbols, rather than the use of a lookup table.
  • the advantage of chemical encryption of information lies in the inherent limitations for the number of trials for deciphering, and the difficulties in copying (which typically requires a physical step).
  • a comparative analysis among additional methods allows determination of the number of meaningful combinations that is feasible in the MolBit-reaction matrix, and thus determine the strength of this bit modifications to secure data storage.
  • Molecular methods that aim to solve hard problems must integrate parallel searching of potential solutions in order to compute with efficiency sufficient.
  • Chemical methods based on Reaction-Diffusion processes are used for solving non-polynomial (NP) complete problems.
  • NP non-polynomial
  • a gel-stamping system comprising a storage, substrate and a stamp gel layer
  • solutions can be defined by chemical concepts of concentration gradients, solubility, or reaction rates, and thus provide an empirical and easy method to solve hard problems.
  • Gel-stamping is a convenient method that use micropatterned agarose gels to control RD. It is a method that enables RD processes in easy-to-fabricate hydrogels, and importantly, parallel processing by imprinting binary, or multilevel architectures into other materials (with features down to 300 nm).
  • Fig. 14A depicts a gel-stamping setup comprising a storage layer, transport layer and a stamp which is used to perform parallelized extraction of a set of acidic dyes (which differ in their acid dissociation constant pKa, ranges from 5-10). Mixtures of these MolBits, imprinted in the storage gel, are immobile because they are poorly soluble in acidic conditions (pH «pKa) and have limited diffusivity.
  • the stamp ‘bulk’ acts as a one-way chemical pump and causes a downwards diffusion of hydroxide ions (red arrow).
  • the inflow of base ultimately deprotonates the acids at the transport-storage interface and causes an upward diffusion of the conjugated bases into the substrate gel (black arrow).
  • the substrate represents the “central processing unit”: it facilitates the transport of the input signal, it integrates the input with the information that is available in the storage gel (which contains a fixed finite number of internal states, that is as large as the input requires), and it visualizes the output (the yellow grid and the blue pattern, Fig. 14C).
  • Subsetting based on differential solubility [0121]
  • the stamp provide variability in the input pH and allows can be used as a ‘filter’ to modify the read out of the pattern in the storage layer.
  • Fig. 14D shows a 3x3 grid, in which three different patterns are encoded using the set of MolBits.
  • the use of different input pH’s ‘selects’ the MolBits based on pKa, read by the total concentration of conjuagted base(s).
  • the concept of parallel subsetting based on pKa is thus similar to the approach of subsetting based on changing the detectability of the MolBits but different in the fact that the subset that is selected is dynamic (the input reaction liberates MolBits from the surface). This feature allows for opportunities to integrate molecules that partition in the substrate.
  • Fig. 15 is a graph of intensity by pH.
  • FIG. 16 a schematic of an example of a computing node is shown.
  • Computing node 10 is only one example of a suitable computing node and is not intended to suggest any limitation as to the scope of use or functionality of embodiments described herein. Regardless, computing node 10 is capable of being implemented and/or performing any of the functionality set forth hereinabove.
  • computing node 10 there is a computer system/server 12, which is operational with numerous other general purpose or special purpose computing system environments or configurations.
  • Examples of well-known computing systems, environments, and/or configurations that may be suitable for use with computer system/server 12 include, but are not limited to, personal computer systems, server computer systems, thin clients, thick clients, handheld or laptop devices, multiprocessor systems, microprocessor-based systems, set top boxes, programmable consumer electronics, network PCs, minicomputer systems, mainframe computer systems, and distributed cloud computing environments that include any of the above systems or devices, and the like.
  • Computer system/server 12 may be described in the general context of computer system-executable instructions, such as program modules, being executed by a computer system.
  • program modules may include routines, programs, objects, components, logic, data structures, and so on that perform particular tasks or implement particular abstract data types.
  • Computer system/server 12 may be practiced in distributed cloud computing environments where tasks are performed by remote processing devices that are linked through a communications network.
  • program modules may be located in both local and remote computer system storage media including memory storage devices.
  • computer system/server 12 in computing node 10 is shown in the form of a general-purpose computing device.
  • the components of computer system/server 12 may include, but are not limited to, one or more processors or processing units 16, a system memory 28, and a bus 18 that couples various system components including system memory 28 to processor 16.
  • Bus 18 represents one or more of any of several types of bus structures, including a memory bus or memory controller, a peripheral bus, an accelerated graphics port, and a processor or local bus using any of a variety of bus architectures.
  • bus architectures include Industry Standard Architecture (ISA) bus, Micro Channel Architecture (MCA) bus, Enhanced ISA (EISA) bus, Video Electronics Standards Association (VESA) local bus, Peripheral Component Interconnect (PCI) bus, Peripheral Component Interconnect Express (PCIe), and Advanced Microcontroller Bus Architecture (AMBA).
  • Computer system/server 12 typically includes a variety of computer system readable media. Such media may be any available media that is accessible by computer system/server 12, and it includes both volatile and non-volatile media, removable and non-removable media.
  • System memory 28 can include computer system readable media in the form of volatile memory, such as random access memory (RAM) 30 and/or cache memory 32.
  • Computer system/server 12 may further include other removable/non-removable, volatile/non-volatile computer system storage media.
  • storage system 34 can be provided for reading from and writing to a non-removable, non-volatile magnetic media (not shown and typically called a "hard drive").
  • a magnetic disk drive for reading from and writing to a removable, non-volatile magnetic disk (e.g ., a "floppy disk")
  • an optical disk drive for reading from or writing to a removable, non-volatile optical disk such as a CD-ROM, DVD-ROM or other optical media
  • each can be connected to bus 18 by one or more data media interfaces.
  • memory 28 may include at least one program product having a set (e.g., at least one) of program modules that are configured to carry out the functions of embodiments of the disclosure.
  • Program/utility 40 having a set (at least one) of program modules 42, may be stored in memory 28 by way of example, and not limitation, as well as an operating system, one or more application programs, other program modules, and program data. Each of the operating system, one or more application programs, other program modules, and program data or some combination thereof, may include an implementation of a networking environment.
  • Program modules 42 generally carry out the functions and/or methodologies of embodiments as described herein.
  • Computer system/server 12 may also communicate with one or more external devices 14 such as a keyboard, a pointing device, a display 24, etc.; one or more devices that enable a user to interact with computer system/server 12; and/or any devices (e.g, network card, modem, etc.) that enable computer system/server 12 to communicate with one or more other computing devices. Such communication can occur via Input/Output (I/O) interfaces 22. Still yet, computer system/server 12 can communicate with one or more networks such as a local area network (LAN), a general wide area network (WAN), and/or a public network (e.g ., the Internet) via network adapter 20.
  • LAN local area network
  • WAN wide area network
  • public network e.g ., the Internet
  • network adapter 20 communicates with the other components of computer system/server 12 via bus 18. It should be understood that although not shown, other hardware and/or software components could be used in conjunction with computer system/server 12. Examples, include, but are not limited to: microcode, device drivers, redundant processing units, external disk drive arrays, RAID systems, tape drives, and data archival storage systems, etc.
  • the present disclosure may be embodied as a system, a method, and/or a computer program product.
  • the computer program product may include a computer readable storage medium (or media) having computer readable program instructions thereon for causing a processor to carry out aspects of the present disclosure.
  • the computer readable storage medium can be a tangible device that can retain and store instructions for use by an instruction execution device.
  • the computer readable storage medium may be, for example, but is not limited to, an electronic storage device, a magnetic storage device, an optical storage device, an electromagnetic storage device, a semiconductor storage device, or any suitable combination of the foregoing.
  • a non- exhaustive list of more specific examples of the computer readable storage medium includes the following: a portable computer diskette, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or Flash memory), a static random access memory (SRAM), a portable compact disc read-only memory (CD-ROM), a digital versatile disk (DVD), a memory stick, a floppy disk, a mechanically encoded device such as punch-cards or raised structures in a groove having instructions recorded thereon, and any suitable combination of the foregoing.
  • RAM random access memory
  • ROM read-only memory
  • EPROM or Flash memory erasable programmable read-only memory
  • SRAM static random access memory
  • CD-ROM compact disc read-only memory
  • DVD digital versatile disk
  • memory stick a floppy disk
  • mechanically encoded device such as punch-cards or raised structures in a groove having instructions recorded thereon
  • a computer readable storage medium is not to be construed as being transitory signals per se, such as radio waves or other freely propagating electromagnetic waves, electromagnetic waves propagating through a waveguide or other transmission media (e.g ., light pulses passing through a fiber-optic cable), or electrical signals transmitted through a wire.
  • Computer readable program instructions described herein can be downloaded to respective computing/processing devices from a computer readable storage medium or to an external computer or external storage device via a network, for example, the Internet, a local area network, a wide area network and/or a wireless network.
  • the network may comprise copper transmission cables, optical transmission fibers, wireless transmission, routers, firewalls, switches, gateway computers and/or edge servers.
  • a network adapter card or network interface in each computing/processing device receives computer readable program instructions from the network and forwards the computer readable program instructions for storage in a computer readable storage medium within the respective computing/processing device.
  • Computer readable program instructions for carrying out operations of the present disclosure may be assembler instructions, instruction-set-architecture (ISA) instructions, machine instructions, machine dependent instructions, microcode, firmware instructions, state-setting data, or either source code or object code written in any combination of one or more programming languages, including an object oriented programming language such as Smalltalk, C++ or the like, and conventional procedural programming languages, such as the “C” programming language or similar programming languages.
  • the computer readable program instructions may execute entirely on the user’s computer, partly on the user’s computer, as a stand-alone software package, partly on the user’s computer and partly on a remote computer or entirely on the remote computer or server.
  • the remote computer may be connected to the user’s computer through any type of network, including a local area network (LAN) or a wide area network (WAN), or the connection may be made to an external computer (for example, through the Internet using an Internet Service Provider).
  • electronic circuitry including, for example, programmable logic circuitry, field- programmable gate arrays (FPGA), or programmable logic arrays (PLA) may execute the computer readable program instructions by utilizing state information of the computer readable program instructions to personalize the electronic circuitry, in order to perform aspects of the present disclosure.
  • These computer readable program instructions may be provided to a processor of a general purpose computer, special purpose computer, or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, create means for implementing the functions/acts specified in the flowchart and/or block diagram block or blocks.
  • These computer readable program instructions may also be stored in a computer readable storage medium that can direct a computer, a programmable data processing apparatus, and/or other devices to function in a particular manner, such that the computer readable storage medium having instructions stored therein comprises an article of manufacture including instructions which implement aspects of the function/act specified in the flowchart and/or block diagram block or blocks.
  • the computer readable program instructions may also be loaded onto a computer, other programmable data processing apparatus, or other device to cause a series of operational steps to be performed on the computer, other programmable apparatus or other device to produce a computer implemented process, such that the instructions which execute on the computer, other programmable apparatus, or other device implement the functions/acts specified in the flowchart and/or block diagram block or blocks.
  • each block in the flowchart or block diagrams may represent a module, segment, or portion of instructions, which comprises one or more executable instructions for implementing the specified logical function(s).
  • the functions noted in the block may occur out of the order noted in the figures.
  • two blocks shown in succession may, in fact, be executed substantially concurrently, or the blocks may sometimes be executed in the reverse order, depending upon the functionality involved.

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Abstract

L'invention concerne des supports de stockage et des procédés de lecture de données à partir desdits supports de stockage et d'écriture de données sur ceux-ci. Des informations sont stockées en tant que mélange de petites molécules (MolBits), disposées dans un réseau d'emplacements adressables sur un substrat. Le mélange comprend au moins deux sous-ensembles de molécules pouvant être identifiées par les différentes propriétés de celles-ci. Dans un mode de réalisation, les informations stockées dans le mélange (1-16) sont décodées par une première étape de séparation de sous-ensembles de Molbits ayant différents facteurs de retard (Rf, I-VIII) sur une plaque de chromatographie sur couche mince. Dans une seconde étape, les sous-ensembles séparés (4, 15 ; 10, 16) peuvent être lus différemment à l'aide de diverses méthodes de visualisation adaptées aux différentes propriétés. Chaque MolBit est associé de manière unique à un emplacement prédéterminé dans une valeur numérique, la présence du MolBit dans le mélange indiquant un chiffre prédéterminé au niveau de l'emplacement associé et l'absence de ladite molécule dans le mélange indiquant un zéro au niveau dudit emplacement associé.
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